Work-aggravated asthma (WAA) is a frequent condition that has been so far overlooked. The broad objective of this program is to improve the diagnosis of WAA and to assess the socio-economic burden of this disease. In order to reach this objective, we propose the following specific aims. 1.To evaluate the proportion of subjects with WAA among the subjects who are referred yearly for possible work-related asthma in two clinics specialized in this field. 2.To compare the clinical, functional and inflammatory characteristics of subjects with WAA, occupational asthma (OA), and asthmatic subjects without WAA nor OA during periods at work and away from work. 3.To evaluate the risk of developing WAA or OA according to the exposure to specific agents at the workplace. 4.To compare the clinical functional and inflammatory outcome of subjects with WAA, OA and asthmatics without WAA nor OA over 2 years and establish prognostic factors for WAA 5.To assess the economic impact of WAA in terms of work disability and use of health resources. Methods. The first part of the study will be of crossover design, with periods of 2 weeks at work and 2 weeks away from work for 3 groups of 60 subjects: subjects with OA, subjects with WAA and asthmatics without WAA nor OA. At the end of each period of time, they will undergo a methacholine challenge and a sputum induction. Next, a specific inhalation challenge will be performed in subjects with work-related asthma to differentiate OA from WAA. Case-control studies will be performed in order to assess which type of occupational agents are likely to induce WAA. The second part of the study will consist in a cohort study with a two-year follow-up of the subjects with OA, WAA and asthmatics without OA not WAA. The subjects will be followed yearly for 2 years by spirometry, methacholine challenge and sputum induction. The occurrence of asthma exacerbations will be recorded. The economic impact of WAA will be assessed in terms of work disability and use of health resources and compared with OA and asthma without OA not WAA.